Metabolic activation of xenobiotic stilbene estrogens

Certain stilbene estrogens, in particular diethylstilbestrol, are established carcinogens in animals and in humans. The question is raised whether the formation of reactive metabolites is part of the carcinogenic mechanism of these compounds. Some aspects of the oxidative metabolism are briefly reviewed, with special emphasis on peroxidase-mediated metabolic activation. The interaction of the reactive intermediates with nucleic acids and proteins is described and examples of the induction of genetic damage in several short-term assays are given. From the available data it is concluded that metabolic activation may play a role in the process of neoplastic cell transformation induced by stilbene estrogens.     

Molecular Modeling of Immunoglobulin Superfamily Proteins: CTLA-4 (CD152) - Comparison of a Predicted and Experimentally Determined Three-Dimensional Structure

The CD28 and CTLA-4 (CD152) receptors on T cells recognize CD80 and CD86 ligands on antigen presenting cells. These interactions provide and control costimulatory signals required for effective T cell activation. CD28 and CTLA-4 belong to the immunoglobulin superfamily (IgSF) and contain a single extracellular ligand binding domain. The three-dimensional (3D) structure of the binding domain of CTLA-4 was modeled previously using a combination of structure-based sequence comparison, IgSF consensus residue analysis, conformational search, and inverse folding calculations. Recently, the 3D structure of CTLA-4 was determined by NMR. Comparison of the modeled and experimentally determined CTLA-4 structure has made it possible to assess the accuracy of our predictions. We found that the overall accuracy of the model was sound and sufficient for a meaningful application of the model in experimental studies. Major errors in the model are limited to the conformation and position of some loops. Our studies on CTLA-4 provide an example for the opportunities and limitations of comparative protein modeling in the presence of low sequence similarity.Electronic Supplementary Material available.     

Oxidative and conjugative metabolism of diethylstilbestrol by rabbit preimplantation embryos

Five- and six-day-old rabbit preimplantation embryos were found to be capable of metabolizing [3H]diethylstilbestrol (DES) in vitro. Based on the analysis of the metabolites formed during a 24-hr incubation period we conclude that these early stage embryos do have active monooxygenase and conjugative activity. The monooxygenase seems to be specific to this early stage of embryonic development.     

Band-shape analysis and display of fine structure in protein spectra: a new approach to perturbation spectroscopy

The shape of light absorption bands of proteins to about 250 nm can be described as the sum of two overlapping lognormal distribution curves. A plot of the differences between the mathematically smooth fitted curve and the experimental points provides a vivid display of vibronic fine structure. Band parameters and difference plots are provided for the N-acetyl-ethyl esters of the aromatic amino acids and are compared with those of glucagon, ribonuclease, chymotrypsinogen, lysozyme and apoaspartate aminotransferase. Changes in band parameters and fine structure are observed upon denaturation and in conversion of glucagon to fibril form.     

Ciprostene in patients with peripheral vascular disease (PVD). An open-label, tolerance trial

Epoprostenol (Prostacyclin) has been studied with various success in patients with peripheral vascular disease (PVD). We investigated the tolerance of a new, stable prostacyclin derivative ciprostene (9-beta-methyl carbacyclin) in 9 PVD patients. The drug was infused intravenously for 8 hours a day, once a week for 4 consecutive weeks, at a dose of 120 ng/kg/min. There were 6 men and 3 women with a mean age of 63 years (42-78). The PVD was verified by arteriography (9 patients) and by clinical findings. Patient #9 was lost to follow up after the first infusion and, consequently, was excluded from further evaluation. In patient #5 with a history of arrhythmias, the last ciprostene infusion had to be discontinued at 4.5 hours due to arrhythmias but his data were included into the evaluation. The cardiac disturbances were not judged to be ciprostene-related. Patients were followed monthly for 3 months after last infusion. Ciprostene was well tolerated although it produced adverse medical events (AMEs); most of them were rated as mild. The most frequent were those typical of prostacyclin: headache, facial flushing and warmth, body warmth, jaw pain and sleepiness. No consistent changes in blood pressure and heart rate were observed. One patient who initially had 9 ischemic ulcers underwent transmetatarsal amputation at month 4. The absolute and relative claudication time was measured by treadmill. As compared to baseline, the absolute claudication time increased significantly at week 2 and 4 of the infusion period and also at the end of month 3, but not at the end of month 4.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oscillations of the NAD(P)H pool size and of the redox state of a cytochrome b during dark respiration of the blue-green alga, Anacystis nidulans

Oscillations of the oxygen uptake rate of the blue-green alga (cyanobacterium) Anacystis nidulans were induced by light pulses. The pool size of NAD(P)H and the redox state of a cytochrome b showed oscillations of similar shape and frequency. Phase diagrams revealed that these three oscillations were presumably linked. The cytochrome b should be a part of the respiratory chain of this blue-green alga. The oscillations were inducible only in a limited physiological state of the alga.     

Uranyl Nitrate Inhibition of Transport Systems in Saccharomyces cerevisiae

Uranyl nitrate inhibited the transport of several amino acids, a vitamin, and a disaccharide into yeast.     

Chemico-nutritional composition of meat of Strombus galeatus (Mesogastropoda: Strombidae)]

Strombus galeatus samples were collected in Lagarto (10 degrees 06'N,85 degrees 48'W), Bahía Ballena (9 degrees 42'N,85 degrees 01'W) and Golfito (8 degrees 30'N,83 degrees 10'W) at the Pacific coast of Costa Rica. Individual weight ranged between 141.9 and 241.3 g (41.3-65.6% edible). Over 72% is water, 23% protein and 3% ash. The caloric content varied between 126.5 and 129 kcal/100g. Fat, crude fiber and carbohydrates contents were small. Mean ranges (%) in minerals were: 403.0-465 P, 233.5-315.7 Ca, 89.7-315.0 K, 122.3-145.5 Na, 217.5-266.3 Mg, 1.5-5.3 Fe, 2.0-8.7 Zn and 0.2-0.5 mg % Cu. As was not detected, and the Cd and Pb contents were 0.046-0.062 and 0.19-0.21 mg/kg, respectively. Concentrations of heavy metals in the meat are not toxic for humans.